Analysis of tyrosine kinases gene mutations in core binding factor related acute myeloid leukemia and its clinical significance / 中华血液学杂志
Chinese Journal of Hematology
; (12): 679-683, 2011.
Article
in Zh
| WPRIM
| ID: wpr-251474
Responsible library:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To assess the prevalence of several tyrosine kinases (TKs) gene mutations including c-Kit, FLT3 and JAK2 V617F in core binding factor related acute myeloid leukemia (CBF-AML), and analyze their impact on clinical characteristics and prognosis.</p><p><b>METHODS</b>Mutations of c-Kit, FLT3-ITD and FLT3-TKD were detected by genomic DNA PCR and sequencing, and JAK2 V617F mutation screening by allele-specific PCR in 58 newly diagnosed CBF-AML patients [28 AML with inv(16) and 30 with t(8;21)], and analyze the patients clinical characteristics and prognoses.</p><p><b>RESULTS</b>c-Kit aberrations were detected in 32.8% cases, including 6 cases mutated in exon 8 (mutKIT8) and 13 mutated in exon 17 (mutKIT17). MutKIT8 was more prominent in inv(16) than in t(8;21) patients (21.4% vs 0, P = 0.009). Only 2 cases had FLT3-ITD and 7 (12.1%) FLT3-TKD mutations. The result of JAK2 V617F mutation screenings in these CBF-AML patients was negative. The frequency of receptor tyrosine kinases(RTK) mutations was 46.6% and only one case had two kinds of missense mutations (mutKIT8 & TKD(+)). Median age of onset was higher for mutKIT17 than for wide-type c-Kit (wtKIT) patients (55 vs 31, P = 0.003). c-Kit mutations were significantly associated with decreased overall survival (OS) and continuous complete remission (CCR) rates (P = 0.053, and 0.048 respectively), and so did more for exon17 mutated patients reduced (P = 0.005, and 0.013 respectively). FLT3-TKD mutation showed no effects on prognosis of CBF-AML patients.</p><p><b>CONCLUSIONS</b>RTK mutations are common in patients with CBF-AML. c-Kit mutations frequently and JAK2V617F mutation rarely appear in CBF-AML. c-Kit mutations, especially mutKIT17 confers higher relapse risk and poorer prognosis.</p>
Full text:
1
Database:
WPRIM
Main subject:
Prognosis
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Protein-Tyrosine Kinases
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DNA Mutational Analysis
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Leukemia, Myeloid, Acute
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Proto-Oncogene Proteins c-kit
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Diagnosis
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Fms-Like Tyrosine Kinase 3
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Core Binding Factors
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Janus Kinase 2
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Genetics
Type of study:
Diagnostic_studies
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Prognostic_studies
Limits:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
Language:
Zh
Journal:
Chinese Journal of Hematology
Year:
2011
Document type:
Article